Neonatal hypoxia–ischemia (HI) is a common complication of pregnancy and delivery. Conventional clinical practice is to resuscitate neonates with 100% O 2 , and evidence is building to suggest resuscitation with lower O 2 concentrations is safer. Significant neurochemical changes are associated with HI injury and persistent changes in amino acids are related to cell death, therefore we used a swine survival model of neonatal HI-reoxygenation (HI/R) to investigate the effects of resuscitation with 100%, 21% or 18% O 2 on amino acid neurotransmitters.In a blinded randomized fashion, following permanent ligation of the left common carotid artery, newborn pigs (1–4 d, 1.7–2.5kg) received alveolar normocapnic hypoxia (FiO 2 =0.15, 2h) and were reoxygenated with 18%, 21% or 100% O 2 . After a 4-day survival period, brain regions were processed for amino acid levels using high-performance liquid chromatography (HPLC).Results showed that resuscitation with different O 2 concentrations caused hemispheric and regional changes in all amino acids investigated including glutamate, alanine, γ-amino butyric acid, glycine and aspartate, 4 days post-HI. Resuscitation with 100% O 2 significantly increased glutamate and glycine in the dorsal cortex contralateral to the ligated common carotid artery, compared to piglets resuscitated with 21% O 2 . Additionally, piglets resuscitated with 21% O 2 had significantly lower alanine levels than those resuscitated with 18% O 2 .Significant resuscitation-dependent changes in amino acid neurotransmitters are still evident 4 days post-HI in the newborn piglet. These data suggest that persistent changes in neurochemistry occur 4 days after HI/R and further studies are warranted to elucidate the consequences of this on neonatal brain development.